Serum complexes of insulin-like growth factor-1 modulate skeletal integrity and carbohydrate metabolism.
Serum insulin-like growth factor (IGF) -1 is secreted mainly by the liver and circulates bound to IGF-binding proteins (IGFBPs), either as binary complexes or ternary complexes with IGFBP-3 or IGFBP-5 and an acid-labile subunit (ALS). The purpose of this study was to genetically dissect the role of IGF-1 circulatory complexes in somatic growth, skeletal integrity, and metabolism. Phenotypic comparisons of controls and four mouse lines with genetic IGF-1 deficits-liver-specific IGF-1 deficiency (LID), ALS knockout (ALSKO), IGFBP-3 (BP3) knockout, and a triply deficient LID/ALSKO/BP3 line-produced several novel findings. 1) All deficient strains had decreased serum IGF-1 levels, but this neither predicted growth potential or skeletal integrity nor defined growth hormone secretion or metabolic abnormalities. 2) IGF-1 deficiency affected development of both cortical and trabecular bone differently, effects apparently dependent on the presence of different circulating IGF-1 complexes. 3) IGFBP-3 deficiency resulted in increased linear growth. In summary, each IGF-1 complex constituent appears to play a distinct role in determining skeletal phenotype, with different effects on cortical and trabecular bone compartments.
Yakar
Shoshana
S
Endocrinology/Diabetes and Bone Disease, The Mt. Sinai School of Medicine, One Gustave L Levy Place, Box 1055, New York, NY 10029-6574, USA. shoshana.yakar@mssm.edu
Rosen
Clifford J
CJ
Bouxsein
Mary L
ML
Sun
Hui
H
Mejia
Wilson
W
Kawashima
Yuki
Y
Wu
Yingjie
Y
Emerton
Kelly
K
Williams
Valerie
V
Jepsen
Karl
K
Schaffler
Mitchell B
MB
Majeska
Robert J
RJ
Gavrilova
Oksana
O
Gutierrez
Mariana
M
Hwang
David
D
Pennisi
Patricia
P
Frystyk
Jan
J
Boisclair
Yves
Y
Pintar
John
J
Jasper
Héctor
H
Domene
Horacio
H
Cohen
Pinchas
P
Clemmons
David
D
LeRoith
Derek
D
D000818:Animals; D001823:Body Composition; D015519:Bone Density / Q000235:genetics / Q000502:physiology*; D001842:Bone and Bones / Q000033:anatomy & histology / Q000502:physiology; D050260:Carbohydrate Metabolism / Q000235:genetics / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D015430:Weight Gain
D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I